The treatment with cardiovascular medical devices enhances survival for many patients with otherwise hopeless medical conditions. Unfortunately, in many cases these devices cause dangerous pathological complications, in particular thrombosis and thromboembolism, which are directly related to non-physiological conditions acting on the blood flowing through these devices. One of the most important design and analysis tools used by bioengineers is computational fluid dynamics (CFD) aided simulation and analysis. With CFD analysis, the fluid induced mechanical stresses through these devices can be computed and assessed. The regions of non-physiologic mechanical shear stresses and stagnant flow in blood flow paths can be precisely identified. The objective of this proposal is to build the link between the dynamics of the shear-induced blood damage and CFD modeling. We propose to examine foundational aspects of flow-induced blood damage hemolysis, platelet activation, cell lysis, and associated byproducts (LDH, aggregates, fragments, coagulation cascade). We will conduct a series of coordinated multi-scale biologic and engineering experiments and link the outcome measures of the blood damage to their mechanistic origins through CFD-based modeling. The specific aims of the proposed project are to: (1) Identify the correlation between CFD-derived fluid-dynamic variables (shear stress, exposure time, flow pattern) and blood damage data (platelet activation, thrombosis, and hemolysis) obtained from human patients and animals implanted with ventricular assist devices (VADs). (2) Develop multi-scale in-vitro experimental platforms to investigate the influence of specific fluid dynamic characteristics on blood cell damage. Using these platforms, generate comprehensive databases of flow-induced blood damage. (3) Based on the collective databases of blood damage, develop and implement a validated CFD model of flow-induced blood damage in a biomedical device. The long-term goal of these studies is to develop accurate, robust, and physiologically realistic numerical models capable of predicting the functional characteristics and bio/hemo-compatibility of cardiovascular devices. The models can aid in the development of new designs in order to improve the functional characteristics and bio/hemo-compatibility of the devices. PUBLIC HEALTH RELEVANCE Blood contacting biomedical devices have played and will continue to play a major role in health care and clinical practice. Continued improvement of these devices relies on multidisciplinary knowledge of medicine, science, and engineering, as well as our persistence in pursuing better technologies. The objective of this proposal is to establish a link between the design and development tool, CFD modeling, and the dynamics of flow-induced blood damage, specifically, hemolysis, platelet activation, cell lysis, and associated byproducts. [unreadable] [unreadable] [unreadable]